TY - JOUR
T1 - Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function
AU - Li, Jie
AU - Zou, Jianqiu
AU - Littlejohn, Rodney
AU - Liu, Jinbao
AU - Su, Huabo
N1 - Funding Information:
We thank Mr. Juan Ayala and Mr. Travis Anderson for proofreading this manuscript. Funding. This study is in part supported by the US National Institutes of Health grants (R01HL124248 to HS, R01HL146807 to JLi, and F31HL139079 to RL) and the American Heart Association grants (19TPA34880050 to HS and 19CDA34760311 to JZ).
Funding Information:
This study is in part supported by the US National Institutes of Health grants (R01HL124248 to HS, R01HL146807 to JLi, and F31HL139079 to RL) and the American Heart Association grants (19TPA34880050 to HS and 19CDA34760311 to JZ).
Publisher Copyright:
© Copyright © 2020 Li, Zou, Littlejohn, Liu and Su.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Defects in protein quality control have been increasingly recognized as pathogenic factors in the development of heart failure, a persistent devastating disease lacking efficacious therapies. Ubiquitin and ubiquitin-like proteins, a family of post-translational modifying polypeptides, play important roles in controlling protein quality by maintaining the stability and functional diversity of the proteome. NEDD8 (neural precursor cell expressed, developmentally downregulated 8), a small ubiquitin-like protein, was discovered two decades ago but until recently the biological significance of NEDD8 modifications (neddylation) in the heart has not been appreciated. In this review, we summarize the current knowledge of the biology of neddylation, highlighting several mechanisms by which neddylation regulates the function of its downstream targets, and discuss the expanding roles for neddylation in cardiac physiology and disease, with an emphasis on cardiac protein quality control. Finally, we outline challenges linked to the study of neddylation in health and disease.
AB - Defects in protein quality control have been increasingly recognized as pathogenic factors in the development of heart failure, a persistent devastating disease lacking efficacious therapies. Ubiquitin and ubiquitin-like proteins, a family of post-translational modifying polypeptides, play important roles in controlling protein quality by maintaining the stability and functional diversity of the proteome. NEDD8 (neural precursor cell expressed, developmentally downregulated 8), a small ubiquitin-like protein, was discovered two decades ago but until recently the biological significance of NEDD8 modifications (neddylation) in the heart has not been appreciated. In this review, we summarize the current knowledge of the biology of neddylation, highlighting several mechanisms by which neddylation regulates the function of its downstream targets, and discuss the expanding roles for neddylation in cardiac physiology and disease, with an emphasis on cardiac protein quality control. Finally, we outline challenges linked to the study of neddylation in health and disease.
KW - Heart Failure
KW - NEDD8 (neural precursor cell expressed developmentally down-regulated 8)
KW - Neddylation
KW - Ubiquitin-like protein
KW - cardiomyopathy
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U2 - 10.3389/fphys.2020.612927
DO - 10.3389/fphys.2020.612927
M3 - Review article
AN - SCOPUS:85098548577
SN - 1664-042X
VL - 11
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 612927
ER -